Yale research links obesity to an miRNA

A team of Yale researchers identified a specific RNA molecule as playing a major influence in the onset of heart disease and obesity.

Carlos Fernandez-Hernando, a professor at the Yale School of Medicine, led the research team, which published its study in the journal Cell Reports on Feb. 20.

“What we found is that when you delete this molecule, you reduce vascular disease and the accumulation of lipids in the arteries,” he said. This collection of lipids contributes to the plaque buildup that causes to heart diseases.

There are many types of RNA, or ribonucleic acid. One in particular, mRNA, serves to carry instructions from an individual’s DNA to the rest of the cell and fulfills an essential role in protein synthesis. MicroRNA molecules, in turn, bind to sequences of mRNA to effectively turn genes on or off.

According to the study, microRNA molecules “have been shown to play an important role in the regulation of nearly all biological processes.”

The study used a mouse model to analyze how the lack of miR-33 — the scientific name for the specific microRNA molecule the researchers investigated — might impact metabolic functions. Mice that completely lacked miR-33 had greater insulin resistance and consumed more food, both of which are symptoms of obesity.

The reason for this, Fernandez-Hernando explained, was that removing the miRNA led to halting the production of cholesterol. While on one hand, the mice did not develop as much plaque in their arteries, on the other, the mice were not able to produce the level of cholesterol necessary for proper liver function.

The researchers interviewed stressed that their study reveals the importance of specifying plaque type, since removal of all plaque was beneficial in some processes and detrimental in others.

Tamas Horvath, the chair of the medical school’s comparative medicine department, described Fernandez-Hernando and his work as a significant presence in the study of RNA.

“He is a major figure in the field and bringing on major evolutions in its understanding,” Horvath said. “What he is bringing to life is that molecules that were less known in the past are playing a fundamental role in biology.”

Nathan Price, another researcher on the team, said that Fernandez-Hernando was the first one to identify miR-33 as a topic for research in 2010.

Since then, he said, gathering information about its role and the effects of modifications to it has been a consistent goal in their lab. The research team has been working on this issue with a mouse model since 2013, Price said.

Horvath explained that this RNA work fit not only into the context of scientific research on RNA, but also into one of the focuses of the comparative medicine department at Yale

“Many of us are interested in obesity and how the epidemic came about to exist,” he said. “We look at how the brain regulates what you eat and how other parts impact that desire during the day and throughout life.”

Though the study’s findings did not come from research on human cells, Fernandez-Hernando said, beginning with a mouse study was an essential part of amassing information and developing new ideas. It allowed the research team to test for the benefits of adjusting miR-33, a molecule present in both organisms.

Almost half of the global population will be overweight by 2025, and a third of these people will be obese, according to the study.